While conventional practice is to discontinue aspirin prior to elective cardiac surgery there is evidence that its continuation may be associated with improved perioperative outcomes. However, uncertainty exists regarding the efficacy of antifibrinolytic agents in the presence of aspirin. We performed a systematic review and meta-analysis of the literature to address the question of the effects of antifibrinolytic agents in cardiac surgery patients maintained on aspirin in terms of both efficacy and adverse events. We conducted an extensive search for randomized controlled trials of antifibrinolytic use in adult patients undergoing coronary artery bypass grafting +/- valve surgery, where aspirin therapy was maintained or initiated through the preoperative period. Data from 17 trials (n=1620) confirmed the efficacy of antifibrinolytic therapy to reduce both chest-tube drainage (weighted mean difference 374 ml, 95% CI 275-473 ml; P<0.00001) and blood transfusion requirements (odds ratio 0.37, 95% CI 0.27-0.49; P<0.00001) in cardiac surgical patients receiving aspirin. We found no difference in the rates of adverse events between groups but observed a trend towards a reduced risk for the composite outcome of thrombotic complications (odds ratio 0.49, 95% CI 0.21-1.13; P=0.09). Antifibrinolytic agents are effective for reducing both chest-tube drainage and transfusion requirements in cardiac surgical patients receiving aspirin. We found no difference between antifibrinolytic and placebo in terms of adverse events but the population was predominantly low-risk. Further studies are required to determine the optimal balance between antiplatelet and antifibrinolytic effects in cardiac surgery.